Mycotic aneurysm and disseminated Mycobacterium avium-intracellulare infection in a patient with hairy cell leukemia.
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Aneurysm, Infected↗
Biomedical subjects
D L Stevens
Publications and source records attributed to D L Stevens.
Lethal effects and cardiovascular effects of purified alpha- and theta-toxins from Clostridium perfringens.
Shock, a common and frequently fatal manifestation of gas gangrene caused by Clostridium perfringens, is probably mediated by extracellular toxins. Previous studies implicating alpha-toxin as the major lethal factor were frequently done with preparations contaminated with a second lethal factor, theta-toxin. We purified alpha- and theta-toxins from C. perfringens and demonstrated that both were lethal to mice. We investigated the effects of these purified toxins on cardiovascular function in intact rabbits; both toxins caused profound hypotension and bradycardia within 40 min. Reduced cardiac output preceded the development of hypotension and bradycardia. Purified alpha-toxin produced a dose-dependent reduction in myocardial function in isolated rabbit atrial preparations. Purified theta-toxin did not directly inhibit myocardial function. Shock induced by alpha-toxin may be partly mediated by direct depression of myocardial function. theta-Toxin reduced cardiac output in intact animals but had no direct effects on isolated heart preparations at concentrations that induced shock in intact animals. These data suggest that theta-toxin-induced shock could be mediated by an endogenous myocardial depressant factor.
Animals↗
The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis.
We investigated the relative efficacies of penicillin, clindamycin, and erythromycin in a mouse model of myositis due to Streptococcus pyogenes. Penicillin was ineffective unless given at the time of bacterial injection, and treatment delays of 2 h reduced its efficacy such that survival was no better than that of untreated control animals (P less than .05). Survival of erythromycin-treated mice was greater than that of both penicillin-treated mice and untreated controls, but only if treatment was begun within 2 h. Mice receiving clindamycin, however, had survival rates of 100%, 100%, 80%, and 70% even if treatment was delayed 0, 2, 6, and 16.5 h, respectively. Thus, clindamycin demonstrated superior efficacy to penicillin among all the various treatment groups (P less than .05). Our results corroborate the failure of penicillin in this model of streptococcal infection and suggest that, unlike penicillin, the efficacy of clindamycin is not adversely altered by the "Eagle effect."
Animals↗
The regulation of synthesis of platelet-activating factor by endothelial cells.
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Animals↗
Spontaneous gas gangrene at a site of remote injury--localization due to circulating antitoxin.
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Adult↗
A natural infection of Fascioloides magna in a llama (Lama glama).
A young, female llama (Lama glama) was euthanized following the onset of hindleg paresis and paralysis. Live trematodes, identified as Fascioloides magna, were identified from the liver of this animal. This represents the first report of F. magna in a llama.
Animals↗
Comparison of clindamycin, rifampin, tetracycline, metronidazole, and penicillin for efficacy in prevention of experimental gas gangrene due to Clostridium perfringens.
Gas gangrene caused by Clostridium perfringens is associated with significant mortality and morbidity in spite of penicillin treatment. Although prompt surgical debridement has been established as the primary therapeutic objective, additional studies are needed for determination of the optimal antimicrobial therapy. In a mouse model of gas gangrene caused by Clostridium perfringens, clindamycin, metronidazole, rifampin, and tetracycline were all more efficacious than penicillin (P less than .05). Survival of penicillin-treated mice was not significantly better than that of untreated controls in spite of serum levels that ranged up to 77-1,800 micrograms/ml. Responses to metronidazole were highly dose dependent. For example, 60% of mice survived after 75 mg of metronidazole/kg, but only 10% survived after 19 mg/kg. In contrast, clindamycin was highly effective over a broad dosing range (8.6-86 mg/kg). The efficacy of all antibiotics was reduced if treatment was delayed or larger inocula of bacteria were used.
Animals↗
Effects of alpha and theta toxins from Clostridium perfringens on human polymorphonuclear leukocytes.
Two toxins, alpha (phospholipase C) and theta (oxygen-labile hemolysin), were purified from Clostridium perfringens type A and assayed for toxic effects on human polymorphonuclear leukocytes (PMNLs). Crude preparations containing both toxins totally inhibited chemotaxis and chemiluminescence responses of PMNLs and reduced PMNL viability. Purified alpha toxin did not alter PMNL viability, chemotactic responsiveness, or morphology but did enhance opsonized zymosan-induced PMNL chemiluminescence over a wide range of toxin concentrations. theta Toxin, at 12.5 hemolytic units (HU) per 10(5) PMNLs, reduced cell viability and induced marked PMNL morphological changes. Concentrations of theta toxin between 4 and 32 HU per 10(5) PMNLs inhibited PMNL chemiluminescence in a dose-dependent manner, whereas a lower concentration enhanced the PMNL chemiluminescent response to opsonized zymosan. Effects on chemotaxis were also dose dependent. Increased PMNL random migration was observed at a concentration of theta toxin of 0.06 HU per 2.5 X 10(5) PMNLs (P less than .05), whereas concentrations of greater than 0.08 HU per 2.5 X 10(5) PMNLs reduced both directed and random migration (P less than .05).
Bacterial Toxins↗
Pseudallescheria boydii arthritis and osteomyelitis in a patient with Cushing's disease.
Pseudallescheria boydii infection involving the left distal femur and knee joint developed in a patient with Cushing's disease, and recurred after treatment with both intravenous miconazole and intravenous amphotericin B. The patient subsequently had synovectomy and arthrodesis, and received ketoconazole, 600 mg per day orally for one year. Concurrent with the start of ketoconazole, a bilateral adrenalectomy was done to control endogenous hypercortisolism. The patient's infection then resolved, and one year afterward there is no clinical or radiologic evidence of recurrent infection.
Adrenalectomy↗
Effect of minimal amounts of thymidine on activity of trimethoprim-sulfamethoxazole against Staphylococcus epidermidis.
The antibacterial activity of trimethoprim-sulfamethoxazole against 99 strains of Staphylococcus epidermidis was tested on media known to be low in thymidine content, as determined by screening with Streptococcus faecalis. Eighty-one percent of the isolates were susceptible by agar dilution. Trimethoprim-sulfamethoxazole was bactericidal against two strains of S. epidermidis when thymidine phosphorylase was added to the medium, indicating utilization of minimal amounts of thymidine that were undetected by screening. Because bacteria vary in their utilization of thymidine and body tissues vary in thymidine content, in vitro susceptibility tests may not correlate with in vivo bactericidal activity.
Anti-Bacterial Agents↗
Effect of antibiotics on toxin production and viability of Clostridium perfringens.
We have recently reported (D.L. Stevens, K.A. Maier, B.M. Laine, and J.E. Mitten, J. Infect. Dis. 155:220-228, 1987) that clindamycin, rifampin, and tetracycline were more efficacious than penicillin in the treatment of fulminant gas gangrene in mice caused by Clostridium perfringens. We hypothesize that antibiotic efficacy correlated with bactericidal or toxin-suppressing properties of these agents. To investigate the possibility that penicillin is only bacteriostatic against C. perfringens, we performed macrobroth dilution MIC and MBC determinations using C. perfringens ATCC 13124. Mean MICs were equal to MBCs for the following antibiotics (micrograms per milliliter): clindamycin, 0.07; tetracycline, 0.05; rifampin, 0.03; metronidazole, 0.69; and penicillin, 0.27. The MIC/MBCs of chloramphenicol were 1.50/3.10 (micrograms/ml). Because antibiotic efficacy did not correlate with bactericidal activity, we measured alpha-toxin activity and found complete suppression of alpha-toxin activity by tetracycline, metronidazole, rifampin, clindamycin, and chloramphenicol at concentrations equal to the MIC. In contrast, alpha-toxin activity persisted at concentrations of penicillin equal to and above the MIC. The dynamics of bacterial killing and kinetics of alpha-toxin production were next studied in log-phase cultures of C. perfringens with antibiotic concentrations 10 times the MIC. Clindamycin, metronidazole, and rifampin all caused rapid reductions in viability, turbidity, and alpha-toxin activity by 15 to 45 min. In contrast, penicillin demonstrated slower bacterial killing, increased turbidity (62.6% of control), and persistent alpha-toxin activity (80% of control values) for 2 h. Tetracycline and chloramphenicol were the least effective in reducing viability; however, the turbidity of cultures did not increase, and alpha-toxin activity was not detectable. Toxin suppression and rapid bacterial killing may in part explain the observed superior therapeutic efficacy of clindamycin, rifampin, and metronidazole compared with penicillin in the treatment of experimental gas gangrene.
Anti-Bacterial Agents↗
Comparison of single and combination antimicrobial agents for prevention of experimental gas gangrene caused by Clostridium perfringens.
The treatment of experimental gas gangrene caused by Clostridium perfringens was investigated by using combinations of antimicrobial agents. This study demonstrated that rifampin, penicillin, metronidazole, and clindamycin were all bactericidal against standard inocula (10(5) to 10(6) CFU). These antimicrobial agents were then administered to mice beginning 30 min after intramuscular injection of 10(9) CFU of C. perfringens type A. The highest doses used produced levels of drug in blood which exceeded the MIC by at least a factor of 40. In addition, other groups of mice received monotherapy at full dose or one-fourth full dose or combination antimicrobial therapy at full or one-fourth full dose. Among the single and combination antimicrobial treatments, metronidazole alone, clindamycin alone, and clindamycin plus penicillin were the most efficacious (P less than 0.05). Although the survival of mice treated with clindamycin plus penicillin was greater than that of mice treated with clindamycin alone, the difference did not reach statistical significance (P greater than 0.05). In contrast, mice treated with a combination of metronidazole and penicillin demonstrated greater mortality than those treated with metronidazole alone (P less than 0.05). In summary, combination antimicrobial therapy of experimental C. perfringens infection did not improve survival compared to that achieved with metronidazole or clindamycin alone, and some combinations significantly reduced survival (P less than 0.05).
Animals↗
Group B streptococcal infection in 1987.
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Female↗
Hepatic necrosis following halothane anesthesia in goats.
One goat anesthetized with thiamylal sodium, xylazine, and halothane for repair of an abominal hernia, and 7 of 29 goats similarly anesthetized for an experiment unrelated to considerations of anesthesia, developed signs of hepatic failure within 24 hours of anesthesia. Affected goats had high values for serum aspartate transaminase and serum total bilirubin by 12 to 24 hours after induction of anesthesia. Necropsy of the 8 affected goats revealed centrilobular to massive hepatic necrosis (8 of 8), brain lesions consistent with hepatic encephalopathy (3 of 4), and acute renal tubular necrosis (6 of 6). Two unaffected goats had no hepatic necrosis. Causes of hepatic necrosis other than those related to anesthesia (eg, infectious agents, toxins) were ruled out by lack of supporting necropsy findings or were considered unlikely because of lack of opportunity for exposure. Hepatic lesions in these goats closely resembled those described in human beings with halothane-associated hepatic injury, although in both species these lesions are nonspecific at the gross and light microscopic levels. The pathogenesis of halothane-associated hepatic injury in goats, as in human beings, remains to be determined.
Anesthesia, General↗
Beta-adrenoceptor-mediated modulation of calcium ionophore activated polymorphonuclear leucocytes.
Beta-adrenoceptor-mediated modulation of calcium-mediated stimulus-response coupling was studied using calcium ionophore (A23187) activation of polymorphonuclear leucocytes (PMNL). Oxygen metabolite generation was measured with luminol- and lucigenin-dependent chemiluminescence in both whole blood and isolated PMNL. Isoprenaline reduced PMNL response by 53% in a dose-dependent fashion. The effect was saturable, stereoselective, antagonized by propranolol and significant at isoprenaline concentrations as low as 0.01 nM. Fifty % maximal response was induced by 0.26 nM, 3 nM, and 125 nM isoprenaline, adrenaline and noradrenaline respectively. Because the effects of beta-adrenoceptor agonists in PMNL have not consistently correlated with measurements of cyclic AMP, alternative means of increasing cyclic AMP were studied. Forskolin and dibutyryl cyclic AMP inhibited PMNL with significant effects at 1.0 microM and 10 microM respectively. The effects of beta-adrenoceptor agonists were much greater when PMNL were activated by calcium ionophore compared with opsonized zymosan. Isoprenaline had no effect upon 1-oleoyl-2-acetylglycerol activated PMNL. Because catecholamine modulation of oxygen metabolite generation can be characterized pharmacologically, PMNL activation by calcium ionophore is an excellent model for study of beta-adrenoceptor function in viable human cells. In contrast to previously described beta-adrenoceptor agonist modulation of PMNL function, inhibition of calcium-mediated activation is significant at physiological concentrations. The clinical consequences of such catecholamine effects are dependent upon the mechanism of PMNL activation in a specific circumstance.
Adrenergic beta-Agonists↗
Comparison of the MicroScan system with the API Staph-Ident system for species identification of coagulase-negative staphylococci.
To evaluate the accuracy of the MicroScan System (American Hospital Supply Corp., Sacramento, Calif.) for identification of coagulase-negative staphylococci, we tested 175 clinical isolates of coagulase-negative staphylococci. The results obtained by the MicroScan system were compared with those of the API Staph-Ident system (Analytab Products, Plainview, N.Y.). Forty-three discrepancies between the two systems were resolved by the conventional method of Kloos and Schleifer (W.E. Kloos and K.H. Schleifer, J. Clin. Microbiol. 1:82-88, 1975). The MicroScan and the Staph-Ident systems correctly identified 146 (86.4%) and 154 (88%) of 175 strains, respectively. The API system failed to identify phosphatase-negative Staphylococcus epidermidis. The MicroScan system demonstrated the greatest accuracy in the identification of S. epidermidis and S. saprophyticus, whereas lesser accuracy was achieved with S. hominis, S. warneri, and S. sciuri.
Bacteriological Techniques↗
Inability of the Chemstrip LN compared with quantitative urine culture to predict significant bacteriuria.
The Chemstrip LN (Boehringer Mannheim Biochemicals, Indianapolis, Ind.), designed to detect pyuria and bacteriuria, was compared with culture of 1,020 unselected, consecutive midstream urine specimens and evaluated on its ability to predict colony counts at three levels. At the level of greater than or equal to 10(5) CFU/ml, the combined test (detection of leukocyte esterase and nitrite) had sensitivity of 82.3%, specificity of 67.9%, positive predictive value of 41.3%, and negative predictive value of 93.3% at prevalence rate of 21.6%. The test would have rejected 9.4% of the specimens with significant bacteriuria if the Chemstrip alone had been used.
Bacteria↗
Fibrogenic potential of intratracheally instilled quartz, ferric oxide, fibrous glass, and hydrated alumina in hamsters.
As a first step in the development of an animal model for determining the role of pulmonary fibrosis in the etiology and pathogenesis of lung cancer, the fibrogenic potential of quartz, quartz and ferric oxide administered together, fibrous glass, and hydrated alumina were studied by multiple intratracheal instillation in groups of male Lak:LVG Syrian golden hamsters. Dose-related decreases in survival were evident for the groups instilled with the two highest doses of quartz or quartz and ferric oxide. Instillation of quartz or quartz and ferric oxide induced the greatest pulmonary fibrosis in response to the materials tested. However, the dense fibrous tissue present in the lungs in classical human silicosis and in experimental silicosis of rats was not observed in this study. The results of this study indicate that the Syrian golden hamster is not a suitable species for studying the role of quartz-induced pulmonary fibrosis in pulmonary carcinogenesis.
Aluminum↗